title: Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice.
abstract: A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities.
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, ON, Canada L8N 3Z5.
authors.forename: Adeel
authors.initials: A
authors.lastname: Safdar
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Bourgeois
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Ogborn
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Little
authors.forename: Bart P
authors.initials: BP
authors.lastname: Hettinga
authors.forename: Mahmood
authors.initials: M
authors.lastname: Akhtar
authors.forename: James E
authors.initials: JE
authors.lastname: Thompson
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Mocellin
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Kujoth
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Prolla
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D004272:DNA, Mitochondrial / Q000235:genetics*; D018628:Gene Dosage; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D017354:Point Mutation
chemical_list: D004272:DNA, Mitochondrial